Our focus has been on the isolation and characterization of genes encoding taste receptors and using these to mark the cells, define the corresponding signaling pathways, dissect receptor specificity, generate topographic maps, and trace the respective neuronal connectivity circuits. This work has identified and characterized two families of G-protein coupled receptors, T1Rs and T2Rs, that are expressed in distinct subsets of taste receptor cells and that include functionally validated sweet, amino acid and bitter taste receptors. In addition, we have shown that the TRP-ion channel PKD2L1 is selectively expressed in sour sensing cells. We have also developed a number of genetically engineered mouse lines that have had a major impact in our understanding of how sweet, bitter and umami taste are encoded at the periphery.[unreadable] [unreadable] In this reporting period, we (in our continuing collaboration with Charles Zuker and his group at UCSD) have studied three aspects of taste at the periphery. In the last reporting period, we identified the cells that respond to sour tastants and the TRP-ion channel PKD2L1 as a candidate sour taste receptor. However, it remained unclear how acid specifically affects these cells and indeed if PKD2L1 is the protein that mediates sour detection. Therefore one focus of our work has been in trying to understand the receptor mechanisms for sour taste and to more precisely determine the role of the PKD2L1 and PKD2L1-expressing cells in taste. The second major focus of our work has been the study of salt taste detection at the periphery. Our recent demonstration that separate classes of taste receptor cells mediate four of the five principle taste modalities (i.e. sweet, sour, bitter and umami or savory taste) opened powerful new avenues to explore salt taste by concentrating on the cells that do not mediate other taste modalities. The third area that we have studied in the past year has been whether other types of stimulus are also mediated through taste. For example, there has recently been considerable focus on whether animals can detect the taste of fat. In addition, other non-conventional tastants have been suggested to stimulate taste receptor cells. We have been studying genetically manipulated animal models to determine the molecular and cellular basis (if any) for these additional types of taste quality.